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Yorodumi- EMDB-7073: Cryo-EM structure of the pancreatic beta-cell KATP channel bound ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7073 | |||||||||
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Title | Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide | |||||||||
Map data | low-pass filtered and sharpened with B-factor of -50, pancreatic beta-cell KATP channel bound to ATP and glibenclamide | |||||||||
Sample |
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Function / homology | Function and homology information Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / cell body fiber / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade ...Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / cell body fiber / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / inward rectifier potassium channel activity / ATPase-coupled monoatomic cation transmembrane transporter activity / nervous system process / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / ankyrin binding / Ion homeostasis / response to ATP / response to testosterone / voltage-gated potassium channel activity / potassium ion import across plasma membrane / action potential / regulation of insulin secretion / potassium channel activity / intercalated disc / axolemma / ABC-type transporter activity / negative regulation of insulin secretion / potassium ion transmembrane transport / T-tubule / heat shock protein binding / positive regulation of protein localization to plasma membrane / potassium ion transport / acrosomal vesicle / regulation of membrane potential / response to ischemia / determination of adult lifespan / cellular response to glucose stimulus / sarcolemma / cellular response to nicotine / glucose metabolic process / nuclear envelope / response to estradiol / cellular response to tumor necrosis factor / presynaptic membrane / transmembrane transporter binding / endosome / response to hypoxia / response to xenobiotic stimulus / neuronal cell body / glutamatergic synapse / apoptotic process / ATP hydrolysis activity / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Cricetus cricetus (black-bellied hamster) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.63 Å | |||||||||
Authors | Martin GM / Yoshioka C / Shyng SL | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Elife / Year: 2017 Title: Anti-diabetic drug binding site in a mammalian K channel revealed by Cryo-EM. Authors: Gregory M Martin / Balamurugan Kandasamy / Frank DiMaio / Craig Yoshioka / Show-Ling Shyng / Abstract: Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been ...Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites. Importantly, the structure shows for the first time that glibenclamide is lodged in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide in our model led to reduced sensitivity to glibenclamide. Our structure provides novel mechanistic insights of how sulfonylureas and ATP interact with the K channel complex to inhibit channel activity. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7073.map.gz | 95.5 MB | EMDB map data format | |
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Header (meta data) | emd-7073-v30.xml emd-7073.xml | 16.3 KB 16.3 KB | Display Display | EMDB header |
Images | emd_7073.png | 78.2 KB | ||
Masks | emd_7073_msk_1.map | 103 MB | Mask map | |
Others | emd_7073_additional.map.gz | 95.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7073 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7073 | HTTPS FTP |
-Validation report
Summary document | emd_7073_validation.pdf.gz | 557.2 KB | Display | EMDB validaton report |
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Full document | emd_7073_full_validation.pdf.gz | 556.7 KB | Display | |
Data in XML | emd_7073_validation.xml.gz | 6.7 KB | Display | |
Data in CIF | emd_7073_validation.cif.gz | 7.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7073 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7073 | HTTPS FTP |
-Related structure data
Related structure data | 6baaMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_7073.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | low-pass filtered and sharpened with B-factor of -50, pancreatic beta-cell KATP channel bound to ATP and glibenclamide | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.855 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_7073_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: unsharpened; unfiltered map of pancreatic beta-cell KATP channel...
File | emd_7073_additional.map | ||||||||||||
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Annotation | unsharpened; unfiltered map of pancreatic beta-cell KATP channel bound to ATP and glibenclamide | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Pancreatic beta-cell ATP-sensitive K+ channel (KATP)
Entire | Name: Pancreatic beta-cell ATP-sensitive K+ channel (KATP) |
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Components |
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-Supramolecule #1: Pancreatic beta-cell ATP-sensitive K+ channel (KATP)
Supramolecule | Name: Pancreatic beta-cell ATP-sensitive K+ channel (KATP) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 950 KDa |
-Supramolecule #2: ATP-sensitive K+ channel subunit Kir6.2
Supramolecule | Name: ATP-sensitive K+ channel subunit Kir6.2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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-Supramolecule #3: ATP-binding cassette sub-family C member 8
Supramolecule | Name: ATP-binding cassette sub-family C member 8 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: ATP-sensitive inward rectifier potassium channel 11
Macromolecule | Name: ATP-sensitive inward rectifier potassium channel 11 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 43.645719 KDa |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) |
Sequence | String: MLSRKGIIPE EYVLTRLAED PTEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMV WWLIAFAHGD LAPGEGTNVP CVTSIHSFSS AFLFSIEVQV TIGFGGRMVT EECPLAILIL IVQNIVGLMI N AIMLGCIF ...String: MLSRKGIIPE EYVLTRLAED PTEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMV WWLIAFAHGD LAPGEGTNVP CVTSIHSFSS AFLFSIEVQV TIGFGGRMVT EECPLAILIL IVQNIVGLMI N AIMLGCIF MKTAQAHRRA ETLIFSKHAV ITPRHGRLCF MLRVGDLRKS MIISATIHMQ VVRKTTSPEG EVVPLHQVDI PM ENGVGGN SIFLVAPLII YHVIDSNSPL YDLAPSDLHH HQDLEIIVIL EGVVETTGIT TQARTSYLAD EILWGQRFVP IVA EEDGRY SVDYSKFGNT VKVPTPLCTA RQLDEDRSLL DALTLASSRG PLRKRSVAVA KAKPKFSISP DSLS |
-Macromolecule #2: ATP-binding cassette sub-family C member 8
Macromolecule | Name: ATP-binding cassette sub-family C member 8 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Cricetus cricetus (black-bellied hamster) |
Molecular weight | Theoretical: 177.333578 KDa |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) |
Sequence | String: MPLAFCGTEN HSAAYRVDQG VLNNGCFVDA LNVVPHVFLL FITFPILFIG WGSQSSKVHI HHSTWLHFPG HNLRWILTFI LLFVLVCEI AEGILSDGVT ESRHLHLYMP AGMAFMAAIT SVVYYHNIET SNFPKLLIAL LIYWTLAFIT KTIKFVKFYD H AIGFSQLR ...String: MPLAFCGTEN HSAAYRVDQG VLNNGCFVDA LNVVPHVFLL FITFPILFIG WGSQSSKVHI HHSTWLHFPG HNLRWILTFI LLFVLVCEI AEGILSDGVT ESRHLHLYMP AGMAFMAAIT SVVYYHNIET SNFPKLLIAL LIYWTLAFIT KTIKFVKFYD H AIGFSQLR FCLTGLLVIL YGMLLLVEVN VIRVRRYIFF KTPREVKPPE DLQDLGVRFL QPFVNLLSKG TYWWMNAFIK TA HKKPIDL RAIAKLPIAM RALTNYQRLC VAFDAQARKD TQSPQGARAI WRALCHAFGR RLILSSTFRI LADLLGFAGP LCI FGIVDH LGKENHVFQP KTQFLGVYFV SSQEFLGNAY VLAVLLFLAL LLQRTFLQAS YYVAIETGIN LRGAIQTKIY NKIM HMSTS NLSMGEMTAG QICNLVAIDT NQLMWFFFLC PNLWTMPVQI IVGVILLYYI LGVSALIGAA VIILLAPVQY FVATK LSQA QRTTLEHSNE RLKQTNEMLR GMKLLKLYAW ESIFCSRVEV TRRKEMTSLR AFAVYTSISI FMNTAIPIAA VLITFV GHV SFFKESDLSP SVAFASLSLF HILVTPLFLL SSVVRSTVKA LVSVQKLSEF LSSAEIREEQ CAPREPAPQG QAGKYQA VP LKVVNRKRPA REEVRDLLGP LQRLAPSMDG DADNFCVQII GGFFTWTPDG IPTLSNITIR IPRGQLTMIV GQVGCGKS S LLLATLGEMQ KVSGAVFWNS NLPDSEGEDP SSPERETAAG SDIRSRGPVA YASQKPWLLN ATVEENITFE SPFNKQRYK MVIEACSLQP DIDILPHGDQ TQIGERGINL SGGQRQRISV ARALYQQTNV VFLDDPFSAL DVHLSDHLMQ AGILELLRDD KRTVVLVTH KLQYLPHADW IIAMKDGTIQ REGTLKDFQR SECQLFEHWK TLMNRQDQEL EKETVMERKA SEPSQGLPRA M SSRDGLLL DEEEEEEEAA ESEEDDNLSS VLHQRAKIPW RACTKYLSSA GILLLSLLVF SQLLKHMVLV AIDYWLAKWT DS ALVLSPA ARNCSLSQEC DLDQSVYAMV FTLLCSLGIV LCLVTSVTVE WTGLKVAKRL HRSLLNRIIL APMRFFETTP LGS ILNRFS SDCNTIDQHI PSTLECLSRS TLLCVSALTV ISYVTPVFLV ALLPLAVVCY FIQKYFRVAS RDLQQLDDTT QLPL VSHFA ETVEGLTTIR AFRYEARFQQ KLLEYTDSNN IASLFLTAAN RWLEVCMEYI GACVVLIAAA TSISNSLHRE LSAGL VGLG LTYALMVSNY LNWMVRNLAD MEIQLGAVKR IHALLKTEAE SYEGLLAPSL IPKNWPDQGK IQIQNLSVRY DSSLKP VLK HVNTLISPGQ KIGICGRTGS GKSSFSLAFF RMVDMFEGRI IIDGIDIAKL PLHTLRSRLS IILQDPVLFS GTIRFNL DP EKKCSDSTLW EALEIAQLKL VVKALPGGLD AIITEGGENF SQGQRQLFCL ARAFVRKTSI FIMDEATASI DMATENIL Q KVVMTAFADR TVVTIAHRVH TILSADLVMV LKRGAILEFD KPETLLSQKD SVFASFVRAD K |
-Macromolecule #3: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 4 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ChemComp-ATP: |
-Macromolecule #4: 5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-...
Macromolecule | Name: 5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-methoxybenzamide type: ligand / ID: 4 / Number of copies: 4 / Formula: GBM |
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Molecular weight | Theoretical: 494.004 Da |
Chemical component information | ChemComp-GBM: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 59417 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |